Protein Dynamics and Flexibility Group

Presentation

Welcome to the web-page of the Protein Dynamics and Flexibility by NMR group at the IBS under the direction of Martin Blackledge.

Conformational dynamics control the biological activity of proteins, thereby regulating the essential processes of life. Protein motion plays a major role in molecular interaction, in the thermodynamic stability of functional states; in molecular recognition processes involving disorder-to-order transitions; and in allostery and molecular signalling, where correlated motions can transmit information between distant sites in a protein.

Nuclear Magnetic Resonance (NMR) spectroscopy is uniquely placed to study a large number of these dynamic processes, resolving detailed and important site-specific information about motions spanning a vast range of time scales in both folded and unfolded proteins, and in both the liquid and the solid phase.

Our key research interests lie in the study of conformational flexibility in proteins in their different forms, and to further our understanding of the complex relationship between molecular motion and biological function and malfunction. Current experiments range from high resolution studies of the conformational energy landscape of folded proteins to the highly flexible behaviour of intrinsically unfolded proteins and their relationship to function.

Key Words

NMR, Conformational flexibility, Intrinsically unstructured proteins, Protein dynamics, Protein structure determination, Protein folding, Functional dynamics.

Key Publications

Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain. M. Wells, H. Tidow, T. J. Rutherford, P. Markwick, M. R. Jensen, E. Mylonas, D. I. Svergun, M. Blackledge*, and A. R. Fersht*. Proc. Natl. Acad. Sci. (U.S.A.)105, 5762Ð5767 (2008).

Highly Populated Turn Conformations in Natively Unfolded Tau Protein Identified from Residual Dipolar Couplings and Molecular Simulation. M. D. Mukrasch, P.R.L. Markwick, J. Biernat, M. von Bergen, P. Bernado, C. Griesinger, E. Mandelkow, M. Zweckstetter and M. Blackledge J.Am.Chem.Soc. 129, 5235-5243 (2007).

Exploring Multiple Timescale Motions in Protein GB3 using Accelerated Molecular Dynamics and NMR. P. Markwick, G. Bouvignies and M. Blackledge J.Am.Chem.Soc. 129, 4724-4730 (2007).

Simultaneous Determination of Protein Structure and Dynamics using Residual Dipolar Couplings. G. Bouvignies, R.Bruschweiler and M. Blackledge. J.Am.Chem.Soc. 128, 15100-15101 (2006).

A structural model for unfolded proteins from residual dipolar couplings and small angle X-ray scattering. P. Bernado, L. Blanchard, P. Timmins, D. Marion, R. Ruigrok and M. Blackledge Proc. Natl. Acad. Sci. (U.S.A.) 102, 17002-17007 (2005)

(A full publication list of the FDP group since 2000 is available here).